Enzyme mimic
Encyclopedia
An enzyme mimic is a small molecule
complex that models the molecular structure, spectroscopic properties, or reactivity of an enzyme
, sometimes called bioinspired complexes.
. Like any other protein an enzyme is an amino acid
polymer
with added cofactors
and other post-translational modifications. Often most of the amino acid polymer is indirectly involved with the enzymes function, perhaps providing ancillary structure or connectivity, indirect activity regulation, or molecular identification of the enzyme. As a result most enzymes are large molecules weighing many kilodaltons. This bulk can obscure various investigative techniques such as NMR
, EPR
, electrochemistry
, crystallography
, among others. It is standard practice to compare spectroscopic data from enzymes to similar spectroscopic data derived from better characterized small molecules. In this way the understanding of metalloenzymes and other metalloprotein
s have developed. In many cases the small molecule analogs were created for other reason, however, it has been increasingly common for group to intentionally make small molecule analogs also known as enzyme mimics. These enzyme mimics are prime examples of bioinorganic chemistry
.
Defining the active site structure. A number of important active sites are still poorly defined. This includes the oxygen evolving complex
and nitrogenase
. In an effort to understand these enzymes small molecule analogs are created and compared to the data which exists for the proteins.
Understanding the active site function. The structure of some enzymes are very well characterized, however, the function of some component of the active site is poorly understood. This is often investigated through site-directed mutagenesis
. In addition the synthesis of a model complex can suggest the function of various components.
Reproducing the enzymes function. A number of enzymes are an interest since they catalyze a reaction chemist find challenging. These reactions include the partial oxidation of a hydrocarbon by methane monooxygenase
(MMO) or the oxidation and production of hydrogen
by hydrogenase
. "Functional" enzyme mimics or bioinspired catalysts are designed with characteristics of the enzyme in hopes of reproducing the enzymes functionality.
Richard Holm
's work on mimics of nitrogenase
and creation of iron sulfur clusters.
Stephen Lippard's work on MMO
.
Christopher Pickett
's work on Hydrogenase mimic
s.
Harry Gray
's work with porphyrin
s complexes.
Small molecule
In the fields of pharmacology and biochemistry, a small molecule is a low molecular weight organic compound which is by definition not a polymer...
complex that models the molecular structure, spectroscopic properties, or reactivity of an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
, sometimes called bioinspired complexes.
Overview
Enzymes are proteins which catalyze a reactionReaction
Reaction may refer to:Response to another event*Adverse drug reaction*Chemical reaction*Emotional reaction*Light reaction*Nuclear reaction*TNA Reaction, a documentary show of TNA behind scenes.*Reaction , as defined by Newton's third law...
. Like any other protein an enzyme is an amino acid
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...
polymer
Polymer
A polymer is a large molecule composed of repeating structural units. These subunits are typically connected by covalent chemical bonds...
with added cofactors
Cofactor (biochemistry)
A cofactor is a non-protein chemical compound that is bound to a protein and is required for the protein's biological activity. These proteins are commonly enzymes, and cofactors can be considered "helper molecules" that assist in biochemical transformations....
and other post-translational modifications. Often most of the amino acid polymer is indirectly involved with the enzymes function, perhaps providing ancillary structure or connectivity, indirect activity regulation, or molecular identification of the enzyme. As a result most enzymes are large molecules weighing many kilodaltons. This bulk can obscure various investigative techniques such as NMR
NMR
NMR may refer to:Applications of Nuclear Magnetic Resonance:* Nuclear magnetic resonance* NMR spectroscopy* Solid-state nuclear magnetic resonance* Protein nuclear magnetic resonance spectroscopy* Proton NMR* Carbon-13 NMR...
, EPR
Electron paramagnetic resonance
Electron paramagnetic resonance or electron spin resonance spectroscopyis a technique for studying chemical species that have one or more unpaired electrons, such as organic and inorganic free radicals or inorganic complexes possessing a transition metal ion...
, electrochemistry
Electrochemistry
Electrochemistry is a branch of chemistry that studies chemical reactions which take place in a solution at the interface of an electron conductor and an ionic conductor , and which involve electron transfer between the electrode and the electrolyte or species in solution.If a chemical reaction is...
, crystallography
Crystallography
Crystallography is the experimental science of the arrangement of atoms in solids. The word "crystallography" derives from the Greek words crystallon = cold drop / frozen drop, with its meaning extending to all solids with some degree of transparency, and grapho = write.Before the development of...
, among others. It is standard practice to compare spectroscopic data from enzymes to similar spectroscopic data derived from better characterized small molecules. In this way the understanding of metalloenzymes and other metalloprotein
Metalloprotein
Metalloprotein is a generic term for a protein that contains a metal ion cofactor. Metalloproteins have many different functions in cells, such as enzymes, transport and storage proteins, and signal transduction proteins. Indeed, about one quarter to one third of all proteins require metals to...
s have developed. In many cases the small molecule analogs were created for other reason, however, it has been increasingly common for group to intentionally make small molecule analogs also known as enzyme mimics. These enzyme mimics are prime examples of bioinorganic chemistry
Bioinorganic chemistry
Bioinorganic chemistry is a field that examines the role of metals in biology. Bioinorganic chemistry includes the study of both natural phenomena such as the behavior of metalloproteins as well artificially introduced metals, including those that are non-essential, in medicine and toxicology...
.
Motivation
Most enyzme mimics studies are motivated by a combination of factors including factors that are unrelated to the enyzme. Several of the factors that are related to the enzyme are listed below.Defining the active site structure. A number of important active sites are still poorly defined. This includes the oxygen evolving complex
Oxygen evolving complex
The oxygen-evolving complex, also known as the water-splitting complex, is a water-oxidizing enzyme involved in the photooxidation of water during the light reactions of photosynthesis. Based on a widely accepted theory from 1970 by Kok, the complex can exist in 5 states: S0 to S4. Photons trapped...
and nitrogenase
Nitrogenase
Nitrogenases are enzymes used by some organisms to fix atmospheric nitrogen gas . It is the only known family of enzymes that accomplish this process. Dinitrogen is quite inert because of the strength of its N-N triple bond...
. In an effort to understand these enzymes small molecule analogs are created and compared to the data which exists for the proteins.
Understanding the active site function. The structure of some enzymes are very well characterized, however, the function of some component of the active site is poorly understood. This is often investigated through site-directed mutagenesis
Site-directed mutagenesis
Site-directed mutagenesis, also called site-specific mutagenesis or oligonucleotide-directed mutagenesis, is a molecular biology technique in which a mutation is created at a defined site in a DNA molecule. In general, this form of mutagenesis requires that the wild type gene sequence be known...
. In addition the synthesis of a model complex can suggest the function of various components.
Reproducing the enzymes function. A number of enzymes are an interest since they catalyze a reaction chemist find challenging. These reactions include the partial oxidation of a hydrocarbon by methane monooxygenase
Methane monooxygenase
Methane monooxygenase, or MMO, is an enzyme capable of oxidizing the C-H bond in methane as well as other alkanes. Methane monooxygenase belongs to the class of oxidoreductase enzymes ....
(MMO) or the oxidation and production of hydrogen
Hydrogen
Hydrogen is the chemical element with atomic number 1. It is represented by the symbol H. With an average atomic weight of , hydrogen is the lightest and most abundant chemical element, constituting roughly 75% of the Universe's chemical elemental mass. Stars in the main sequence are mainly...
by hydrogenase
Hydrogenase
A hydrogenase is an enzyme that catalyses the reversible oxidation of molecular hydrogen . Hydrogenases play a vital role in anaerobic metabolism....
. "Functional" enzyme mimics or bioinspired catalysts are designed with characteristics of the enzyme in hopes of reproducing the enzymes functionality.
Significant Examples
This list is extremely abbreviated in terms of the enzymes mimicked and the primary investigators working on each enzyme mimic.Richard Holm
Richard H. Holm
Richard Hadley Holm , also known as R. H. Holm, is an American inorganic chemist.Professor Holm received his Ph.D. from the Massachusetts Institute of Technology in 1959 under the direction of F. Albert Cotton. After the completion of his degree, he joined the chemistry faculty at Harvard University...
's work on mimics of nitrogenase
Nitrogenase
Nitrogenases are enzymes used by some organisms to fix atmospheric nitrogen gas . It is the only known family of enzymes that accomplish this process. Dinitrogen is quite inert because of the strength of its N-N triple bond...
and creation of iron sulfur clusters.
Stephen Lippard's work on MMO
Methane monooxygenase
Methane monooxygenase, or MMO, is an enzyme capable of oxidizing the C-H bond in methane as well as other alkanes. Methane monooxygenase belongs to the class of oxidoreductase enzymes ....
.
Christopher Pickett
Christopher Pickett
Christopher Arthur Pickett was an English cricketer. Pickett was a left-handed batsman who bowled slow left-arm orthodox as well as left-arm fast. He was born in Hedgerley, Buckinghamshire....
's work on Hydrogenase mimic
Hydrogenase mimic
-Overview:The fields of molecular biology and inorganic chemistry overlap in the study of metalloenzymes in the form of enzyme mimics among other. The advantage of indirect modeling or enzyme mimicry is high-resolution crystal structures and well-defined spectral data from which comparisons can be...
s.
Harry Gray
Harry B. Gray
Harry Barkus Gray is the Arnold O. Beckman Professor of Chemistry at California Institute of Technology. He won the Priestley Medal in 1991, Harvey Prize in 2000, The Benjamin Franklin Medal in Chemistry in 2004, and the Wolf Prize in Chemistry in 2004.-Career:Gray received his B.S...
's work with porphyrin
Porphyrin
Porphyrins are a group of organic compounds, many naturally occurring. One of the best-known porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin. Porphyrins are heterocyclic macrocycles composed of four modified pyrrole subunits interconnected at...
s complexes.